Sequential Infusion of Mesenchymal Stem Cell for Graft-Versus-Host Disease Prevention in Haploidentical Hematopoietic Stem Cell Transplantation: An Open-Label, Multicenter, Randomized Controlled Clinical Trial
Han Yao, Ruihao Huang, Haixia Fu, Ren Lin, Yanqi Zhang, Yimei Feng, Yu Wang, Ting Chen, Xiaoqi Wang, Lidan Zhu, Jia Liu, Yuqing Liu, Lu Zhao, Lu Wang, Peiyan Kong, Wen Qin, Cheng Zhang, Li Gao, Lei Gao, Qifa Liu, Xiaohui Zhang, Xiao‐Jun Huang, Xi Zhang
Abstract
PURPOSE The aim of this open-label, multicenter, randomized controlled trial was to determine the efficacy and safety of sequential umbilical cord–derived mesenchymal stem cell (UC-MSC) infusion for graft-versus-host disease (GVHD) prevention within 3 months of haploidentical hematopoietic stem cell transplantation (haplo-HSCT). METHODS This open-label study evaluated UC-MSC infusion (administer 1 × 10 6 /kg 4 hours before the commencement of day 0, once weekly for the first month after transplantation, once every 2 weeks for the second month, and once during the third month, totaling eight doses). The primary end point was the 2-year cumulative incidence of severe chronic GVHD (cGVHD). RESULTS In the primary analysis, 192 qualified participants between age 18 and 60 years with haplo-HSCT in three transplant centers in China were enrolled and randomly assigned to the MSC and control groups. In the primary analysis, the estimated 2-year cumulative incidence of severe cGVHD and all grades of cGVHD was lower in the MSC group than in the control group ( P = .033 and P = .022). The cumulative incidence of grade 1 to 4, 2 to 4, and 3 to 4 acute GVHD (aGVHD) in patients in the MSC group significantly decreased (all P < .001). The 3-year GVHD-free and relapse-free survival (GRFS) rate in the MSC group was 62.4%, which was significantly higher than that in the control group (32.0%, hazard ratio [HR], 0.34, P < .001). MSC infusion did not influence the cumulative incidence of relapse ( P = .34) and nonrelapse mortality ( P = .45). CONCLUSION Our findings suggest that sequential infusion of MSCs within 3 months after haplo-HSCT significantly reduced both the incidence and severity of cGVHD and aGVHD, manifesting as a better GRFS rate for patients.